Throughout this application various publications are referred to in parentheses. Full citations for these references may be found at the end of the specification before the claims. The disclosures of these publications are hereby incorporated by reference in their entireties into the subject application to more fully describe the art to which the subject application pertains.
Arthritis is a leading cause of pain and disability. Osteoarthritis (OA) affects over 27 million Americans (1,2) and is a great economic burden in the United States with over $185.5 billion in annual medical care expenditures (3-7). The number of subjects suffering from arthritis is expected to grow to over 67 million by 2030. The growth is credited to an increased aging population and increased prevalence of obesity. Within this population, 29.8% of the 45-64 age group report doctor-diagnosed arthritis and 50% of persons aged 65 or older are diagnosed with osteoarthritis. While 16.4% of under/normal weight adults report doctor-diagnosed arthritis, 52.5% of arthritis patients are overweight or obese. Furthermore, patients who suffered from joint injury currently account for 12% of all OA cases, which is approximately 5.6 million in the United States.
Several treatments are available for osteoarthritis, including physical therapy, pharmacological therapies such as glucosamine sulfate, chondroitin sulfate, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, weak opioids or other analgesics, and finally end-stage disease management and surgery (8). However, there is currently no cure for osteoarthritis nor do current therapies effectively slow or arrest its progression (5,9). Moreover, many of the pharmacological agents used to treat osteoarthritis are associated with detrimental gastrointestinal, renal, and cardiovascular side effects with long term use (10-12). There are also many nutraceutical-based compounds (e.g. turmeric/curcumin, green tea, glucosamine, hyaluronic acid) marketed to treat joint pain and arthritis, but their effectiveness in treating OA have not been clearly demonstrated, and none of these supplements have been approved by the FDA to treat or cure disease (13). While current therapeutic approaches may relieve pain and some disease symptoms, they may fail to prevent or slow the progression of osteoarthritis because they do not adequately correct the pathological alterations in specific cellular and molecular pathways that are responsible for the disease.
The present invention addresses the need for improved treatments for arthritis, such as osteoarthritis and rheumatoid arthritis, where the treatments are safe, effective and suitable for decades-long treatment.